title: Drug efficacy by direct and adjusted indirect comparison to placebo: An illustration by Mycobacterium avium complex prophylaxis in HIV.
abstract: BACKGROUND
  Our goal was to illustrate a method for making indirect treatment comparisons in the absence of head-to-head trials, by portraying the derivation of published efficacies for prophylaxis regimens of HIV-related opportunistic infections.
  
  
  RESULTS
  We identified published results of randomized controlled trials from the United States in which HIV-infected patients received rifabutin, azithromycin, clarithromycin, or placebo for prophylaxis against Mycobacterium avium complex (MAC). We extracted the number of subjects, follow-up time, primary MAC events, mean CD4 count, and proportion of subjects on mono or dual antiretroviral therapy (ART) from each study. We derived the efficacy of each drug using adjusted indirect comparisons and, when possible, by direct comparisons. Five articles satisfied our inclusion criteria. Using direct comparison, we estimated the efficacies of rifabutin, clarithromycin, and azithromycin compared to placebo to be 53% (95% CI, 48-61%), 66% (95% CI, 61-74%), and 66% (95% CI, 60-81%), respectively. Using adjusted indirect calculations, the efficacy of rifabutin compared to placebo ranged from 41% to 44%. The adjusted indirect efficacies of clarithromycin and azithromycin were estimated to be 73% and 72%, respectively.
  
  
  CONCLUSIONS
  Accurate estimates of specific drug dosages as compared to placebo are important for policy and implementation research. This study illustrates a simple method of adjusting for differences in study populations by using indirect comparisons in the absence of head-to-head HIV clinical trials.
authors.affiliation: Division of General Medicine, Department of Medicine, Massachusetts General Hospital, Boston, USA. jchu6@partners.org.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chu
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Sloan
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Freedberg
authors.forename: Yazdan
authors.initials: Y
authors.lastname: Yazdanpanah
authors.forename: Elena
authors.initials: E
authors.lastname: Losina